Scientist seeks to enhance memory, brainpower

This is your brain at age 20. It does a fairly good job of learning and remembering.

This is your brain at age 60. Wouldn’t it be great if it worked just as well?

Gary Lynch, AS ’65, thinks he may have found a way to accomplish exactly that, through his pioneering research with a class of drugs called ampakines. Lynch, a renowned neuroscientist who conducts research at the University of California, Irvine (UCI), returned to the UD campus in April to deliver the 2008 Grass Traveling Scientist Lecture for the Delaware chapter of the Society of Neuroscience.

The New Castle, Del., native first enrolled at the University as an engineering major, then left for a time (“I was a bit wild,” he says) before returning to study psychology. He opened his talk by referring to his interrupted undergraduate experience.
“There was a time when I wondered if the University of Delaware would ever let me back,” he said with a smile. “My career here was spotty.”

Lynch, however, found success at UD as a psychology major. He went on to attend graduate school at Princeton University, where he earned his doctoral degree just three years after enrolling. At UCI, Lynch is professor of psychiatry and human behavior and publishes extensively in academic journals. Beginning in the 1970s, he has published 20 or more papers per decade that are among the most frequently cited papers by other researchers in his field.

His focus has been on the biochemical mechanism of memory, seeking to understand how memory is created in the brain and how it deteriorates with age and in such conditions as Huntington’s and Alzheimer’s diseases.

“In biology, if you think you understand the underpinnings of something, you think you can change it,” Lynch said in his talk. Research, he said, has shown that the human brain operates at nowhere near its optimal capacity: “There’s lots of room for improvement.”

Lynch and colleagues have been studying the brain’s neocortex, the center of higher mental functions, which he described as “an incredibly complex network” of billions of neurons, all sending electrical messages to communicate with one another. In the 1990s, the UCI researchers developed ampakines, a new class of drugs that “attach to each of these little receptors and amplify their function,” he said.

Ampakines have received attention in the popular press as well as the scientific community, touted as “smart pills” by USA Today, “concentration in a bottle” by Time magazine and “memory pills for the forgetful” by the BBC. While human trials are in their early stages, with the initial emphasis on treatment for attention deficit-hyperactivity disorder (ADHD) rather than memory-loss conditions, Lynch described promising research by his lab and others on the effect of ampakines on rats and monkeys.

Some highlights he discussed:

• Rats using particular odors to learn how to navigate a maze were able to cut their learning time in half when given injections of ampakines. In other words, a task that usually took 10 tries to master was learned in only five tries after the injections.
  
  
• In the same type of exercise, young rats learned much more quickly than middle-aged rats. But, once the older rats were given ampakines, they performed as well as the youngsters.
  
  
• Rats that were “overtrained,” practicing a task so many times they had clearly reached their capacity for learning it and their performance had leveled off, began learning again and improving their performance after receiving ampakines.
  
  
• Similar results were found in tests where monkeys observed, remembered and later recalled images they were shown on a computer screen.
  

The higher levels of learning and memory continued after the ampakines injections were stopped and after the drugs were no longer in the body.

Scans showed that more neurons were firing in the brains of the monkeys receiving the drugs, with the animals utilizing areas of the brain that weren’t being accessed before, Lynch said.

“They’re not just growing bigger networks [of neurons],” he said. “They’re actually adding more networks. I wish I had data like this in humans.”

Ampakines have been tested in ADHD and sleep deprivation, and trials in Alzheimer’s disease are beginning, Lynch said. Because the drugs work by correcting synapse problems (the points where neurons connect and communicate) and therefore improving memory, he said, they have potential use in such conditions as Huntington’s, mental retardation, normal aging and estrogen loss.

“I don’t know if these drugs…are the right approach, the final approach,” Lynch said. “But I know that this approach has opened the door.”

The next step, in addition to more clinical trials of ampakines, is to further open the door to memory enhancement by conducting research to map areas of the brain and determine where memory is located, Lynch said.

Such mapping is important, he said, “because, without being able to map the distribution of memory in the brain, how can we fix it?”

Lynch, who joined UCI in 1969, is a co-founder of Cortex Pharmaceutical, a biotech company that holds the exclusive license from UCI for its patents on ampakines. His research has been funded by grants from such agencies as the National Institute on Aging, the National Institute of Neurological Disorders and Stroke and the National Institute of Mental Health. He is a member of the Neuroscience Society and the International Brain Research Organization.

—Ann Manser, AS ’73